pH- and temperature-induced release of doxorubicin from multilayers of poly(2-isopropyl-2-oxazoline) and tannic acid

Abstract

We present a simple strategy to prepare doxorubicin (DOX) containing hydrogen-bonded films of poly(2-isopropyl-2-oxazoline) (PIPOX) and tannic acid (TA) which release DOX in acidic conditions while releasing a minimal amount of DOX at physiological pH. Water soluble complexes of TA and DOX (TA − DOX) were prepared prior to film construction. PIPOX and TA − DOX were deposited at the surface at pH 6.5 using the layer-by-layer (LbL) technique. We found that multilayers released a minimal amount of DOX at physiological pH due to further ionization of TA with increasing pH and enhanced electrostatic interactions between TA and DOX. In contrast, pH-induced release of DOX was observed in moderately acidic conditions due to protonation of TA as the acidity increased and electrostatic interactions between TA and DOX decreased. Moreover, we found that raising the temperature from 25 ∘ C to 37.5 ∘ C increased the amount of DOX released from the surface. This can be rationalized with the conformational changes within the multilayers correlated with the lower critical solution temperature behaviour of PIPOX and increased kinetic energy of DOX molecules. Considering the acidic nature of tumour tissues and important biological properties of PIPOX and TA, these multilayers are promising for pH-and temperature-triggered release of DOX from surfaces.

Layer‐By‐Layer Modified Superparamagnetic Iron Oxide Nanoparticles with Stimuli‐Responsive Drug Release Properties

“…However, the release at 42 °C was remarkably greater than that at 25 °C and 37 °C and increased steeply up to 4 h. This difference can be correlated with the conformational transition of PIPOX chains from extended to globular above its LCST leading to the formation of void‐like structures within the PIPOX layer which possibly facilitated DOX release from the multilayers. Different from these results, we recorded temperature‐induced drug release from 40‐bilayer PIPOX multilayers even at 37 °C in a recent study by our group . The reason for not getting a remarkable temperature response from TA/PIPOX coated SPIONs surface at 37 °C might be due to lower amount of PIPOX within the coating (only 1‐layer PIPOX within 3‐layer film).…”

“…Poly(2‐alkyl‐2‐oxazoline)s exhibit important biological properties, for example, biocompatibility, nontoxicity, antifouling, and stealth behavior . Among poly(2‐alkyl‐2‐oxazoline)s, PIPOX is of interest for biomedical applications due to its LCST‐type phase behavior around 36 °C .…”

“…Poly(2-alkyl-2-oxazoline)s exhibit important biological properties, for example, biocompatibility, nontoxicity, antifouling, and stealth behavior. [27][28][29][30][31][32] Among poly(2-alkyl-2-oxazoline)s, PIPOX is of interest for biomedical applications due to its LCSTtype phase behavior around 36 °C. [33] TA is a natural polyphenol and also displays important biological properties such as antitumor, antioxidant, antibacterial, antienzymatic and antimutagenic activities.…”

Preparation of Layer‐by‐Layer Films with Remarkably Different pH‐Stability and Release Properties Using Dual Responsive Block Copolymer Micelles

“…Sukhishvili reported earlier on increased permeability of thymol blue from multilayers of a LCST‐type polymer at increasing temperature . We have also previously reported the effect of temperature on the release of functional molecules from the multilayers containing polymers with LCST …”

“…[60] We have also previously reported the effect of temperature on the release of functional molecules from the multilayers containing polymers with LCST. [61,62]…”